The present invention relates to a method for distinguishing between calcified atherosclerotic tissue and fibrous atherosclerotic tissue or normal cardiovascular tissue using Raman spectroscopy.
It is well known that deposits of plaque on cardiovascular tissues, such as on the interior walls of arteries, can severely restrict or completely block the flow of blood therethrough. Such plaque typically exits in two forms, namely, as calcified plaque or as fibrous plaque. Calcified plaque is more rigid and more difficult to remove than fibrous plaque.
As can readily be appreciated, methods for detecting deposits of calcified plaque and/or fibrous plaque on blood vessels have substantial utility in the diagnosis and treatment of atherosclerosis and related cardiovascular ailments.
In U.S. Pat. No. 4,785,806 to Deckelbaum, which is incorporated herein by reference, a process and apparatus for ablating atherosclerotic tissue is disclosed. The process comprises directing a low power ultraviolet laser having a wavelength outside the band of visible wavelengths at a selected section of a blood vessel to cause fluorescence of the tissue in said section, analyzing the frequency spectrum of such fluorescence to determine whether the section of the blood vessel at which said low power laser is directed is normal or atherosclerotic, providing a high power laser having an output in the form of pulses, the pulse duration and pulse energy per unit area of said pulses being selected so as to cause ablation without charring, directing the pulses from said high power laser at said section if said step of analyzing the frequency spectrum indicates that said section is atherosclerotic, continuing to irradiate the tissue with said low power ultraviolet laser energy to cause said tissue to fluoresce, and discontinuing the laser ablation process when the fluorescence pattern of the tissue indicates that it is no longer atherosclerotic.
In U.S. Pat. No. 4,718,417 to Kittrell et al., there is also disclosed a method for diagnosis of the type of tissue in an artery, including distinguishing artery wall from atheromateous plaque using visible fluorescence spectral information.
While the above-described processes are suitable for detecting fibrous atherosclerotic tissue, they cannot be used to detect calcified atherosclerotic tissue since calcified atherosclerotic tissue and normal cardiovascular tissue have indistinguishable fluorescence spectra.
A variety of spectroscopic methods for detecting calcified atherosclerotic tissue are described by R. H. Clarke et al. in "Spectroscopic Characterization of Cardiovascular Tissue," Lasers in Surgery and Medicine, Vol. 8, pp. 45-59 (1988). In particular, Clarke et al. discuss using visible Raman spectroscopy to analyze the surface of diseased and healthy tissue sites on postmortem specimens of calcified aortic valve leaflets and coronary artery segments.
In "Raman Spectroscopy of Atherosclerotic Plaque: Implications for Laser Angioplasty," Radiology, Vol. 177, pp. 262 (Nov. 1990 Supplement), Redd et al. disclose using visible Raman spectroscopy to analyze human cadaveric aorta, percutaneous peripheral atherectomy, and surgical endarterectomy samples and conclude that Raman spectroscopy allows fatty plaque to be distinguished from a normal artery.
One disadvantage to using visible light to illuminate biological materials for analysis by Raman spectroscopy as described above is that a significant fluorescence background is usually obtained. Consequently, to obtain the Raman spectrum, one must assume the fluorescence profile and subtract it from any observed signal. This method is inaccurate and difficult to use.
In "Applications of Near-Infrared Fourier Transform Raman Spectroscopy in Biology and Medicine," Spectroscopy, Vol. 5, No. 7, pp. 24-32 (1990), Nie et al. disclose that fluorescence-free Raman spectra were obtained from pigmented squirrel eye lenses, normal and cataracious human eye lenses, intact bones and teeth, various woody tissues, human and chicken sclera, blood vessels, liver tissue, muscles, cartilage and tobacco mosaic virus using near-infrared Fourier Transform (FT) Raman spectroscopy.
In "Human Breast Tissue Studied by IR Fourier Transform Raman Spectroscopy," Lasers in the Life Sciences, Vol. 4, No. 1, pp. 1-6 (1991), Alfano et al. disclose that fluorescence-free Raman spectra of benign breast tissues, benign tumor tissues, and malignant tumor tissues were obtained using IR FT Raman spectroscopy, and note that the difference in the relative intensity between the 1445 and 1651 cm.sup.-1 Raman lines, as well as the number of Raman lines in the different tissues, offers a potentially new optical diagnostic to detect cancer.